Novel ester containing compositions and methods

Abstract

Described herein are compositions (e.g., a pharmaceutical composition) and methods for controlling the delivery of a therapeutic agent, and their use in the treatment and/or prevention of diseases and disorders.

What is claimed: 
     
         1 . A composition of esters, the composition comprising an α-hydroxy carboxylic acid ester, a second ester, and a third ester, wherein the α-hydroxy carboxylic acid ester, the second ester, and the third ester are not the same; and wherein less than 10% of the composition comprises fatty alcohols and/or alkyl lactyllactate and/or other related substances. 
     
     
         2 . The composition of  claim 1 , wherein the second ester is a compound of formula (I):
 second ester is a compound of formula (I):   
       
         
           
           
               
               
           
         
         wherein 
         each R 1  is independently selected from the group consisting of: H, C 1 -C 20  straight chained or branched alkyl, C 3 -C 10  cycloalkyl, substituted C 1 -C 20  alkyl, arylalkyl, aryl, substituted aryl and heteroaryl; 
         each R 2  is independently selected from the group consisting of: H and C 1 -C 20  alkyl; 
         R 3  is a C 12 -C 40  alkyl; and 
         X is NR 1 R 1  or OR 1 ; 
       
     
     
         3 . The composition of  claim 1 , wherein the α-hydroxy carboxylic acid ester is a compound of formula (II): 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2  and R 3  are as defined in formula (I). 
       
     
     
         4 . The composition of  claim 2 , wherein the second ester is a compound of formula (II): 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2  and R 3  are as defined in formula (I). 
       
     
     
         5 . The composition of  claim 1 , wherein the α-hydroxy carboxylic acid ester and the second esters are compounds of formula (II): 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2  and R 3  are as defined in formula (I). 
       
     
     
         6 - 7 . (canceled) 
     
     
         8 . The composition of  claim 1 , further comprising a fourth ester. 
     
     
         9 . The composition of  claim 8 , wherein the α-hydroxy carboxylic acid ester, the second ester, the third ester and the fourth ester are not the same. 
     
     
         10 . The composition of  claim 8 , further comprising a fifth ester. 
     
     
         11 . The composition of  claim 10 , wherein the α-hydroxy carboxylic acid ester, the second ester, the third ester, the fourth ester and the fifth are not the same. 
     
     
         12 . The composition of  claim 1 , having less than 5% of the composition comprises fatty alcohols and/or alkyl lactyllactate and/or other related substances. 
     
     
         15 . The composition of  claim 12 , substantially free of fatty alcohols and/or alkyl lactyllactate and/or other related substances. 
     
     
         16 . The composition of  claim 1 , wherein the α-hydroxy carboxylic acid ester, the second ester, the third ester, the fourth ester and/or the fifth ester is present in an enantiomeric excess of the R stereoisomer. 
     
     
         17 . The composition of  claim 1 , wherein the α-hydroxy carboxylic acid ester, the second ester, the third ester, the fourth ester and/or the fifth ester is present in an enantiomeric excess of the S stereoisomer. 
     
     
         18 . The composition of  claim 1 , wherein the composition is a pharmaceutical composition. 
     
     
         19 . The composition of  claim 1 , wherein the composition is configured for topical administration or in the form of a patch. 
     
     
         20 . The composition of  claim 1 , wherein the composition is in the form of an oil-in-water emulsion, a water-in-oil emulsion, a thickened aqueous gel, a hydrophilic gel or hydrophobic gel. 
     
     
         21 . The composition of  claim 1 , consisting essentially of an α-hydroxy carboxylic acid ester and a second ester, wherein the esters are not the same. 
     
     
         22 . The composition of  claim 1 , consisting of an α-hydroxy carboxylic acid ester and a second ester, wherein the esters are not the same. 
     
     
         23 . The composition of  claim 1 , further comprising a drug. 
     
     
         24 . The composition of  claim 23 , wherein the drug is selected from the group consisting of aclometasone, acyclovir, alitretinoin, alprostadil, amcinonide, amlexanox, anthralin, azelaic acid, bacitracin, becaplermin, betamethasone, betamethasone valerate, benzocaine, benzoyl peroxide, budenoside, bupivacaine, buprenorphine, bupropion, butenafine, butoconazole, calcipotriene, calcitriol, capsaicin, celecoxib, chlorhexidene gluconate, ciclopirox, clindamycin, clobetasol propionate, clocortilone, clotrimazole, crotamiton, dehydroergotamine, desonide dipropionate, desoximetasone, desoximetasone pivalate, disulfuram, diazepam, dibucaine, diclofenac, diflorasone diacetate, diflunisal, diphenhydramine, donepezil, doxepin, erythromycin, famciclovir, fentanyl, fluandrenolide, flucinolone acetonide, flucinonide, flunisolide, fluorouracil, fluoxetine, fluticasone, fluticasone propionate, fluvoxamine, glycolic acid, halcinonide, halobetasol propionate, hydrocodone, hydrocortisone, hydrocortisone valerate, hydroxyzine, ibuprofen, imiquimod, indomethacin, isosorbide dintrate, ketoconazole, ketoprofen, ketorolac, lidocaine, lindane, mafenide acetate, meperidine, metoclopramide, metronidazole, miconazole, mometasone, mometasone furoate, morphine, mupirocin, naftifine, naloxone, naltrexone, naproxen, neomycin, nitroglycerin, nystatin, ondansetron, oxiconazole, oxycodone, paroxetine, penciclovir, permethrin, phenylephrine, piperonyl butoxide, piroxicam, podofilox, polymyxin, pramoxine, prilocaine, prochlorperazine, promethazine, pyrethrins, rofecoxib, scopolamine, sertraline, sildenafil, sufentanil, sulindac, sumatriptan, tacrine, tacrolimus, tadalafil, tazarotene, terbinafine, terconazole, testosterone, tioconazole, tolnaftate, trazodone, tretinoin, tramcinolone, triazolam, valacyclovir, vardenafil, varenicline, zolpidem 
     
     
         25 . The composition of  claim 1 , wherein the α-hydroxy carboxylic acid ester and second ester are present in a ratio of 99:1 to 1:99. 
     
     
         26 - 86 . (canceled) 
     
     
         87 . A method of providing a composition having a preselected value for a parameter rated to penetration, the method comprising:
 selecting a value for the parameter;   selecting a mixture having of esters, the mixture having a relative amount of an α-hydroxy carboxylic acid ester and a second ester so as to provide for the selected value.   
     
     
         88 . The method of  claim 87 , wherein the second ester is a compound of formula (I):
 second ester is a compound of formula (I):   
       
         
           
           
               
               
           
         
         wherein 
         each R 1  is independently selected from the group consisting of: H, C 1 -C 20  straight chained or branched alkyl, C 3 -C 10  cycloalkyl, substituted C 1 -C 20  alkyl, arylalkyl, aryl, substituted aryl and heteroaryl; 
         each R 2  is independently selected from the group consisting of: H and C 1 -C 20  alkyl; 
         R 3  is a C 12 -C 40  alkyl; and 
         X is NR 1 R 1  or OR 1 . 
       
     
     
         89 . The method of  claim 87 , wherein the α-hydroxy carboxylic acid ester is a compound of formula (II): 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2  and R 3  are as defined in formula (I). 
       
     
     
         90 . The method of  claim 88 , wherein the second ester is a compound of formula (II): 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2  and R 3  are as defined in formula (I). 
       
     
     
         91 . The method of  claim 87 , wherein the α-hydroxy carboxylic acid ester and the second esters are compounds of formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2  and R 3  are as defined in formula (I). 
       
     
     
         92 - 97 . (canceled)